Virulence. 2023 May 23:2215602. doi: 10.1080/21505594.2023.2215602. Online ahead of print.

ABSTRACT

BACKGROUND: Mycobacterium abscessus subspecies massiliense (M. massiliense) is increasingly recognized as an emerging bacterial pathogen, particularly in cystic fibrosis (CF) patients and CF centers' respiratory outbreaks. We characterized genomic and phenotypic changes in 15 serial isolates from two CF patients (1S and 2B) with chronic pulmonary M. massiliense infection leading to death, as well as four isolates from a CF center outbreak in which patient 2B was the index case.

RESULTS: Comparative genomic analysis revealed the mutations affecting growth rate, metabolism, transport, lipids (loss of glycopeptidolipids), antibiotic susceptibility (macrolides and aminoglycosides resistance), and virulence factors. Mutations in 23S rRNA, mmpL4, porin locus and tetR occurred in isolates from both CF patients.Interestingly, we identified two different spontaneous mutation events at the mycobacterial porin locus: a fusion of two tandem porin paralogs in patient 1S and a partial deletion of the first porin paralog in patient 2B. These genomic changes correlated with reduced porin protein expression, diminished 14C-glucose uptake, slower bacterial growth rates, and enhanced TNF-α induction in mycobacteria-infected THP-1 human cells. Porin gene complementation of porin mutants partly restored 14C-glucose uptake, growth rate and TNF-α levels to those of intact porin strains.

CONCLUSIONS: We hypothesize that specific mutations accumulated and maintained over time in M. massiliense, including mutations shared among transmissible strains, collectively lead to more virulent, host adapted lineages in CF patients and other susceptible hosts.

PMID:37221835 | DOI:10.1080/21505594.2023.2215602

J Steroid Biochem Mol Biol. 2023 May 20:106332. doi: 10.1016/j.jsbmb.2023.106332. Online ahead of print.

ABSTRACT

Patients with cystic fibrosis (CF) commonly have lower circulating concentrations of 25-hydroxyvitamin D (25(OH)D) than healthy populations. We comprehensively compared measures of vitamin D metabolism among individuals with CF and healthy control subjects. In a cross-sectional study, serum from participants with CF (N=83) and frequency-matched healthy control subjects by age and race (N=82) were analyzed for: 25(OH)D2 and 25(OH)D3, 1α,25-dihydroxyvitamins D2 and D3 (1α,25(OH)2D2 and 1α,25(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), 4β,25-dihydroxyvitamin D3 (4β,25(OH)2D3), 25-hydroxyvitamin D3-3-sulfate (25(OH)D3-S), and 25-hydroxyvitamin D3-3-glucuronide (25(OH)D3-G). In a 56-day prospective pharmacokinetic study, ~25μg deuterium-labeled 25(OH)D3 (d6-25(OH)D3) was administered intravenously to participants (N=5 with CF, N=5 control subjects). Serum was analyzed for d6-25(OH)D3 and d6-24,25(OH)2D3, and pharmacokinetic parameters were estimated. In the cross-sectional study, participants with CF had similar mean (SD) total 25(OH)D concentrations as control subjects (26.7 [12.3] vs. 27.7 [9.9] ng/mL) and had higher vitamin D supplement use (53% vs. 22%). However, participants with CF had lower total 1α,25(OH)2D (43.6 [12.7] vs. 50.7 [13.0] pg/mL), 4β,25(OH)2D3 (52.1 [38.9] vs. 79.9 [60.2] pg/mL), and 25(OH)D3-S (17.7 [11.6] vs. 30.1 [12.3] ng/mL) (p < 0.001 for all). The pharmacokinetics of d6-25(OH)D3 and d6-24,25(OH)D3 did not differ between groups. In summary, although 25(OH)D concentrations were comparable, participants with CF had lower 1α,25(OH)2D, 4β,25(OH)2D3, and 25(OH)D3-S concentrations than healthy controls. Neither 25(OH)D3 clearance, nor formation of 24,25(OH)2D3, appears to account for these differences and alternative mechanisms for low 25(OH)D in CF (i.e., decreased formation, altered enterohepatic recirculation) should be explored.

PMID:37217104 | DOI:10.1016/j.jsbmb.2023.106332

J Hum Genet. 2023 May 22. doi: 10.1038/s10038-023-01160-2. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.

PMID:37217688 | DOI:10.1038/s10038-023-01160-2

Sci Rep. 2023 May 22;13(1):8228. doi: 10.1038/s41598-023-32216-0.

ABSTRACT

Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

PMID:37217548 | DOI:10.1038/s41598-023-32216-0

J Cyst Fibros. 2023 May 20:S1569-1993(23)00134-0. doi: 10.1016/j.jcf.2023.05.004. Online ahead of print.

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) is characterized in stages: never (prior to first positive culture) to incident (first positive culture) to chronic. The association of Pa infection stage with lung function trajectory is poorly understood and the impact of age on this association has not been examined. We hypothesized that FEV1 decline would be slowest prior to Pa infection, intermediate after incident infection and greatest after chronic Pa infection.

METHODS: Participants in a large US prospective cohort study diagnosed with CF prior to age 3 contributed data through the U.S. CF Patient Registry. Cubic spline linear mixed effects models were used to evaluate the longitudinal association of Pa stage (never, incident, chronic using 4 different definitions) with FEV1 adjusted for relevant covariates. Models contained interaction terms between age and Pa stage.

RESULTS: 1,264 subjects born 1992-2006 provided a median 9.5 (IQR 0.25 to 15.75) years of follow up through 2017. 89% developed incident Pa; 39-58% developed chronic Pa depending on the definition. Compared to never Pa, incident Pa infection was associated with greater annual FEV1 decline and chronic Pa infection with the greatest FEV1 decline. The most rapid FEV1 decline and strongest association with Pa infection stage was seen in early adolescence (ages 12-15).

CONCLUSIONS: Annual FEV1 decline worsens significantly with each Pa infection stage in children with CF. Our findings suggest that measures to prevent chronic infection, particularly during the high-risk period of early adolescence, could mitigate FEV1 decline and improve survival.

PMID:37217389 | DOI:10.1016/j.jcf.2023.05.004

Front Pediatr. 2023 May 5;11:943649. doi: 10.3389/fped.2023.943649. eCollection 2023.

ABSTRACT

Exocrine pancreatic insufficiency (EPI) is a condition defined as pancreatic loss of exocrine function, including decreased digestive enzymes and bicarbonate secretion, which leads to maldigestion and malabsorption of nutrients. It is a common complication in many pancreatic disorders. If left undiagnosed, EPI can cause poor digestion of food, chronic diarrhea, severe malnutrition and related complications. Nutritional status and fat-soluble vitamins should be carefully assessed and monitored in patients with EPI. Early diagnosis of EPI is clinically important for appropriate nutritional support and initiating pancreatic enzyme replacement therapy (PERT) which could significantly improve patient outcomes. The evaluation of nutritional status and related unique management in children with EPI will be discussed in this review.

PMID:37215591 | PMC:PMC10196508 | DOI:10.3389/fped.2023.943649

Res Sq. 2023 May 10:rs.3.rs-2846739. doi: 10.21203/rs.3.rs-2846739/v1. Preprint.

ABSTRACT

Background Treatment of cystic fibrosis (CF) has been revolutionized by the use of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy. Prior studies support a role for type 2 (T2) inflammation in many people with CF (PwCF) and CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We hypothesized that ETI initiation decreases T2 inflammation in PwCF. Methods A single center retrospective chart review was conducted for adult PwCF. As markers of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E (IgE) data were collected longitudinally 12 months prior to ETI therapy initiation and 12 months following therapy initiation. Multivariable analyses adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid use, and microbiological colonization. Results There was a statistically significant reduction (20.10%, p < 0.001) in 12-month mean IgE following ETI initiation; this change remained statistically significant in the multivariate model. The longitudinal analysis demonstrated no change in AEC following therapy initiation. Conclusion This study shows reduction in IgE but no change in AEC after ETI therapy initiation. We think that the lack of influence on AEC argues against an impact on previously established T2 inflammation and that the reduction in IgE is likely related to antigen load reduction post ETI. Further studies are warranted to determine the underlying mechanism of ETI impact on T2 inflammation and possible role for asthma immunomodulator therapy post ETI initiation in CFAOS.

PMID:37215020 | PMC:PMC10197784 | DOI:10.21203/rs.3.rs-2846739/v1

Front Digit Health. 2023 May 4;5:1196442. doi: 10.3389/fdgth.2023.1196442. eCollection 2023.

ABSTRACT

Cystic Fibrosis (CF) is a chronic life-limiting condition that affects multiple organs within the body. Patients must adhere to strict medication regimens, physiotherapy, diet, and attend regular clinic appointments to manage their condition effectively. This necessary but burdensome requirement has prompted investigations into how different digital health technologies can enhance current care by providing the opportunity to virtually monitor patients. This review explores how virtual monitoring has been harnessed for assessment or performance of physiotherapy/exercise, diet/nutrition, symptom monitoring, medication adherence, and wellbeing/mental-health in people with CF. This review will also briefly discuss the potential future of CF virtual monitoring and some common barriers to its current adoption and implementation within CF. Due to the multifaceted nature of CF, it is anticipated that this review will be relevant to not only the CF community, but also those investigating and developing digital health solutions for the management of other chronic diseases.

PMID:37214343 | PMC:PMC10192704 | DOI:10.3389/fdgth.2023.1196442

Porto Biomed J. 2022 Oct 24;7(5):e194. doi: 10.1097/j.pbj.0000000000000194. eCollection 2022 Sep-Oct.

ABSTRACT

INTRODUCTION: Children/adolescents with cystic fibrosis (CF) have psychological and physical difficulties that have a severe impact on their health-related quality of life (HRQoL).

AIM: To evaluate the impact of CF on HRQoL in a pediatric age sample by identifying major determinants and comparing the HRQoL reports of children and their parents.

METHODS: A sample of 27 children/adolescents was included in a cross-sectional observational study. Inclusion criteria were age between 4 and 18 years, diagnosis of CF, and the attendance of a caregiver in patients younger than 14 years. A questionnaire was applied to assess sociodemographic data and nutritional status. HRQoL was evaluated using the Portuguese revised version of the CF questionnaire (CFQ-R). Spearman correlations were calculated to analyze the agreement between children's and parents' reports. Spearman correlations and Mann-Whitney U tests were performed to identify associations between HRQoL domains and determinants.

RESULTS: The scores of CFQ-R domains were high, with the lowest median value being 66.67. It was found positive moderate associations between children's and parents' reports in 3 domains (P < .05): eating disturbances, body image, and respiratory symptoms. The median scores were similar in the eating disturbances (approximately 80.00) and in the respiratory symptoms (83.33). However, there is a consistent difference of 14.07 in the body image domain. Current age, physical activity, and iron were positively associated with HRQoL, whereas age at diagnosis was negatively associated.

CONCLUSION: These findings reinforce the importance to evaluate HRQoL during childhood and adolescence and to invest in this public health theme.

PMID:37213921 | PMC:PMC10194718 | DOI:10.1097/j.pbj.0000000000000194

Front Neurol. 2023 May 5;14:1200101. doi: 10.3389/fneur.2023.1200101. eCollection 2023.

ABSTRACT

Intestinal motility disorders represent a frequent problem in children with neurological impairment. These conditions are characterized by abnormal movements of the gut, which can result in symptoms such as constipation, diarrhea, reflux, and vomiting. The underlying mechanisms leading to dysmotility are various, and the clinical manifestations are often nonspecific. Nutritional management is an important aspect of care for children with gut dysmotility, as it can help to improve their quality of life. Oral feeding, when safe and in the absence of risk of ingestion or severe dysphagia, should always be encouraged. When oral nutrition is insufficient or potentially harmful, it is necessary to switch to an enteral by tube or parenteral nutrition before the onset of malnutrition. In most cases, children with severe gut dysmotility may require feeding via a permanent gastrostomy tube to ensure adequate nutrition and hydration. Drugs may be necessary to help manage gut dysmotility, such as laxatives, anticholinergics and prokinetic agents. Nutritional management of patients with neurological impairment often requires an individualized care plan to optimize growth and nutrition and to improve overall health outcomes. This review tries to sum up most significant neurogenetic and neurometabolic disorders associated with gut dysmotility that may require a specific multidisciplinary care, identifying a proposal of nutritional and medical management.

PMID:37213895 | PMC:PMC10196023 | DOI:10.3389/fneur.2023.1200101

Curr Opin Pediatr. 2023 May 22. doi: 10.1097/MOP.0000000000001259. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Glucose metabolism alterations in cystic fibrosis range from the classic cystic fibrosis-related diabetes (CFRD) to forms of glucose intolerance and prediabetes. The aim of the present work is to review the most up-to-date novelties in terms of CFRD diagnosis and therapy. This review is timely and relevant because it allows an update for the early and correct classification of glucose abnormalities in cystic fibrosis and because it favours an appropriate therapeutic approach.

RECENT FINDINGS: Confirm that Oral Glucose Tolerance Test is still the diagnostic gold standard despite the advent of continuous glucose monitoring (CGM) systems; this latter is spreading very rapidly, however, to date, there is still no strong evidence to hypothesize the use of CGM for diagnostic purposes. CGM has indeed proven to be very useful in managing and guiding CFRD therapy.

SUMMARY: Tailored and personalized insulin therapy is still the recommended therapy for children and adolescents with CFRD, although nutritional intervention and oral hypoglycaemic treatment are equally important and efficacious. Finally CFTR modulators have allowed the increase of the life expectancy of cystic fibrosis patients and have proven effective not only in improving the pulmonary function and the nutritional status but also the glucose control.

PMID:37211992 | DOI:10.1097/MOP.0000000000001259

J Chemother. 2023 May 21:1-7. doi: 10.1080/1120009X.2023.2213600. Online ahead of print.

ABSTRACT

The Achromobacter species is an emerging pathogen causing chronic bacterial infections in patients with certain conditions, such as cystic fibrosis (CF), hematologic and solid organ malignancies, renal failure, and certain immune deficiencies. In the present study, we assessed the in vitro bactericidal activities of eravacycline, either alone or in combination with colistin, meropenem, or ceftazidime, using 50 Achromobacter spp. strains isolated from CF patients. We also investigated the synergistic interactions of these combinations using microbroth dilutions against 50 strains of Achromobacter spp. Bactericidal, and we assessed the synergistic effects of the tested antibiotic combinations using the time-kill curve (TKC) technique. Our studies show that meropenem alone is the most effective antibiotic of those tested. Based on the TKCs, we found that eravacycline-colistin combinations display both bactericidal and synergistic activities for 24 h against 5 of the 6 Achromobacter spp. strains, including colistin-resistant ones, at 4xMIC of colistin. Although we did not observe synergistic interactions with eravacycline-meropenem or eravacycline-ceftazidime combinations, we did not observe antagonism with any combination tested.This study's findings could have important implications for antimicrobial therapy with tested antibiotics.

PMID:37211830 | DOI:10.1080/1120009X.2023.2213600

J Glob Antimicrob Resist. 2023 May 19:S2213-7165(23)00082-6. doi: 10.1016/j.jgar.2023.05.006. Online ahead of print.

ABSTRACT

OBJECTIVE: Cystic fibrosis (CF) is a hereditary recessive disease that affects the mucous clearance of the lungs and allows bacteria such as Staphylococcus aureus to settle in the lung and cause infection. This study examined the prevalence of antibiotic resistance of S. aureus in cystic fibrosis infection using a systematic review and meta-analysis.

METHOD: A comprehensive and systematic search of related articles was conducted through the PubMed, Scopus, and Web of Science databases until March 2022. The weighted pooled resistance rate (WPR) of antibiotics was analyzed with Freeman-Tukey double arcsine transformation in the Stata software version 17.1 using the Metaprop command.

RESULTS: In this meta-analysis, 25 studies were used based on criteria to evaluate the pattern of S. aureus resistance in CF. Vancomycin and teicoplanin were the most effective options of treatment for CF patients', although the highest antibiotic resistance to erythromycin and clindamycin was observed.

CONCLUSION: High resistance to most of the antibiotics studied was observed. The high levels of antibiotic resistance observed are worrisome and indicate the need to monitor antibiotic use.

PMID:37211214 | DOI:10.1016/j.jgar.2023.05.006

Angew Chem Int Ed Engl. 2023 May 21:e202300585. doi: 10.1002/anie.202300585. Online ahead of print.

ABSTRACT

Chemical communication between competing bacteria in multi-species environments often enables both species to adapt and survive, and perhaps even thrive. P. aeruginosa and S. aureus are two bacterial pathogens found in natural biofilms, especially in the lungs of cystic fibrosis (CF) patients, where recent studies showed that there is often cooperation between the two species, leading to increased disease severity and antibiotic resistance. However, the mechanisms behind this cooperation are poorly understood. In this study, we analyzed co-cultured biofilms in various settings, and we applied untargeted mass spectrometry-based metabolomics analyses, combined with synthetic validation of candidate compounds. We unexpectedly discovered that S. aureus can convert pyochelin into pyochelin methyl ester, an analogue of pyochelin with reduced affinity for iron (III). This conversion allows S. aureus to coexist more readily with P. aeruginosa and unveils a mechanism underlying the formation of robust dual-species biofilms.

PMID:37211536 | DOI:10.1002/anie.202300585

J Cyst Fibros. 2023 May 19:S1569-1993(23)00128-5. doi: 10.1016/j.jcf.2023.04.022. Online ahead of print.

ABSTRACT

Short chain fatty acids (SCFA) are produced by anaerobic bacteria. The most common SCFAs are acetate, propionate and butyrate. SCFAs have been implicated in several inflammatory diseases including cystic fibrosis (CF) where they are present in the airways at millimolar concentrations. Staphylococcus aureus is one of the main respiratory pathogens in CF. Polymorphonuclear neutrophil granulocytes (PMN) represent the most important immune defense the host uses against S. aureus. However, the reason why PMNs are unable to clear S. aureus in CF remains largely unclear. We hypothesized that SCFAs impair effector functions of PMNs in response to S. aureus. To test this, human PMNs were exposed to CF clinical isolates of S. aureus in vitro in the presence or absence of SCFAs and effector functions of PMNs were assessed. Our data show that SCFAs do not affect the viability of PMNs and do not stimulate the release of neutrophil extracellular traps (NET) from human PMNs. Production of reactive oxygen species (ROS), another important antimicrobial function of PMNs, on the other hand, was significantly inhibited by SCFAs in response to the bacterium. SCFAs did not compromise the ability of PMNs to kill CF isolates of S. aureus in vitro. Overall, our results provide new knowledge into the interactions between SCFAs and the immune system, and indicate that SCFAs produced by anaerobic bacteria in the CF lung could interfere with reactive oxidant production of PMNs in response to S. aureus, one of the prominent respiratory pathogens in this disease.

PMID:37211502 | DOI:10.1016/j.jcf.2023.04.022

BMC Med Res Methodol. 2023 May 20;23(1):121. doi: 10.1186/s12874-023-01947-z.

ABSTRACT

BACKGROUND: There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of endpoints and improve their selection in rare disease clinical studies, reducing the risk of patient misclassification.

METHODS: Neutral theory was used to assess the accuracy of rare disease clinical study endpoints and the resulting probability of false positive and false negative classifications at different disease prevalence rates. Search strings were extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021. Overall, 11 rare diseases with one disease-specific disease severity scale (133 studies) and 12 rare diseases with more than one disease-specific disease severity scale (483 studies) were included. All indicators from clinical studies were extracted, and Neutral theory was used to calculate their match to disease-specific disease severity scales, which were used as surrogates for the disease phenotype. For those with more than one disease-severity scale, endpoints were compared with the first disease-specific disease severity scale and a composite of all later scales. A Neutrality score of > 1.50 was considered acceptable.

RESULTS: Around half the clinical studies for half the rare diseases with one disease-specific disease severity score (palmoplantar psoriasis, achalasia, systemic lupus erythematosus, systemic sclerosis and Fournier's gangrene) met the threshold for an acceptable match to the disease phenotype, one rare disease (Guillain-Barré syndrome) had one study with an acceptable match, and four diseases (Behcet's syndrome, Creutzfeldt-Jakob disease, atypical hemolytic uremic syndrome and Prader-Willi syndrome) had no studies. Clinical study endpoints in almost half the rare diseases with more than one disease-specific DSS (acromegaly, amyotrophic lateral sclerosis, cystic fibrosis, Fabry disease and juvenile rheumatoid arthritis) were a better match to the composite, while endpoints in the remaining rare diseases (Charcot Marie Tooth disease, Gaucher disease Type I, Huntington's disease, Sjogren's syndrome and Tourette syndrome) were a worse match. Misclassifications varied with increasing disease prevalence.

CONCLUSIONS: Neutral theory confirmed that disease-severity measurement needs improvement in rare disease clinical studies, especially for some diseases, and suggested that the potential for accuracy increases as the body of knowledge on a disease increases. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical studies may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.

PMID:37210484 | DOI:10.1186/s12874-023-01947-z

Pulmonology. 2023 May 18:S2531-0437(23)00088-0. doi: 10.1016/j.pulmoe.2023.03.008. Online ahead of print.

NO ABSTRACT

PMID:37210338 | DOI:10.1016/j.pulmoe.2023.03.008

J Cyst Fibros. 2023 May 18:S1569-1993(23)00135-2. doi: 10.1016/j.jcf.2023.05.005. Online ahead of print.

NO ABSTRACT

PMID:37210228 | DOI:10.1016/j.jcf.2023.05.005

J Cyst Fibros. 2023 May 17:S1569-1993(23)00138-8. doi: 10.1016/j.jcf.2023.05.008. Online ahead of print.

ABSTRACT

Clinical trials are a necessary tool for evaluating the effectiveness of newly developed treatments and interventions for cystic fibrosis (CF). Prior work demonstrated a proportional underrepresentation of people with CF (pwCF) identifying as part of a minoritized racial or ethnic group in clinical trials. In order to establish a baseline for improvement efforts, we undertook a center-level self-study to evaluate if the racial and ethnic backgrounds of pwCF participating in clinical trials at our CF Center in New York City reflect our overall patient diversity (N = 200; 55 pwCF identifying as part of a minoritized racial or ethnic group and 145 pwCF identifying as non-Hispanic White). A smaller proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a clinical trial as compared to pwCF identifying as non-Hispanic White (21.8% vs. 35.9%, P = 0.06). A similar trend was present for pharmaceutical clinical trials (9.1% vs. 16.6%, P = 0.3). When limiting the study population to the pwCF most likely to be eligible for a CF pharmaceutical clinical trial, a larger proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a pharmaceutical clinical trial as compared to pwCF identifying as non-Hispanic White (36.4% vs. 19.6%, P = 0.2). No pwCF identifying as part of a minoritized racial or ethnic group participated in an offsite clinical trial. Efforts to improve the racial and ethnic diversity of pwCF in clinical trials, both onsite and offsite, will require a shift in how recruitment opportunities are identified and communicated to pwCF.

PMID:37208235 | DOI:10.1016/j.jcf.2023.05.008

J Cyst Fibros. 2023 May 17:S1569-1993(23)00137-6. doi: 10.1016/j.jcf.2023.05.007. Online ahead of print.

NO ABSTRACT

PMID:37208234 | DOI:10.1016/j.jcf.2023.05.007